Investigating the Effects of Sex Hormones on Macrophage Polarization
Sex differences in the development and progression of cardiovascular disease are well established, but the effects of sex hormones on macrophage polarization and pro-atherogenic functions are not well described. We hypothesize that sex hormones directly modulate macrophage polarization, and thereby...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/2/951 |
| _version_ | 1797339825409359872 |
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| author | Sophie Enright Geoff H. Werstuck |
| author_facet | Sophie Enright Geoff H. Werstuck |
| author_sort | Sophie Enright |
| collection | DOAJ |
| description | Sex differences in the development and progression of cardiovascular disease are well established, but the effects of sex hormones on macrophage polarization and pro-atherogenic functions are not well described. We hypothesize that sex hormones directly modulate macrophage polarization, and thereby regulate the progression of atherosclerosis. Bone marrow-derived monocytes from adult male and female C57BL/6 mice were differentiated into macrophages using macrophage colony-stimulating factor (20 ng/mL) and pre-treated with either 17β-estradiol (100 nM), testosterone (100 nM), or a vehicle control for 24 h. Macrophages were polarized into pro- or anti-inflammatory phenotypes and the effects of sex hormone supplementation on the gene expression of macrophage phenotypic markers were assessed using RT-qPCR. Inflammatory markers, including IL-1β, were quantified using an addressable laser bead immunoassay. A transwell migration assay was used to determine changes in macrophage migration. Sex differences were observed in macrophage polarization, inflammatory responses, and migration. Pre-treatment with 17β-estradiol significantly impaired the gene expression of inflammatory markers and the production of IL-1β in inflammatory macrophages. In anti-inflammatory macrophages, 17β-estradiol significantly upregulated the expression of anti-inflammatory markers and enhanced migration. Pre-treatment with testosterone enhanced anti-inflammatory mRNA expression and impaired the production of IL-1β. Our observations suggest a protective role of 17β-estradiol in atherogenesis that may contribute to the sexual dimorphisms in cardiovascular disease observed in human patients. |
| first_indexed | 2024-03-08T09:53:59Z |
| format | Article |
| id | doaj.art-93dbd92b22ea40b9b1a47283ee716bc0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T09:53:59Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-93dbd92b22ea40b9b1a47283ee716bc02024-01-29T13:55:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-0125295110.3390/ijms25020951Investigating the Effects of Sex Hormones on Macrophage PolarizationSophie Enright0Geoff H. Werstuck1Thrombosis and Atherosclerosis Research Institute, 237 Barton Street E, Hamilton, ON L8L 2X2, CanadaThrombosis and Atherosclerosis Research Institute, 237 Barton Street E, Hamilton, ON L8L 2X2, CanadaSex differences in the development and progression of cardiovascular disease are well established, but the effects of sex hormones on macrophage polarization and pro-atherogenic functions are not well described. We hypothesize that sex hormones directly modulate macrophage polarization, and thereby regulate the progression of atherosclerosis. Bone marrow-derived monocytes from adult male and female C57BL/6 mice were differentiated into macrophages using macrophage colony-stimulating factor (20 ng/mL) and pre-treated with either 17β-estradiol (100 nM), testosterone (100 nM), or a vehicle control for 24 h. Macrophages were polarized into pro- or anti-inflammatory phenotypes and the effects of sex hormone supplementation on the gene expression of macrophage phenotypic markers were assessed using RT-qPCR. Inflammatory markers, including IL-1β, were quantified using an addressable laser bead immunoassay. A transwell migration assay was used to determine changes in macrophage migration. Sex differences were observed in macrophage polarization, inflammatory responses, and migration. Pre-treatment with 17β-estradiol significantly impaired the gene expression of inflammatory markers and the production of IL-1β in inflammatory macrophages. In anti-inflammatory macrophages, 17β-estradiol significantly upregulated the expression of anti-inflammatory markers and enhanced migration. Pre-treatment with testosterone enhanced anti-inflammatory mRNA expression and impaired the production of IL-1β. Our observations suggest a protective role of 17β-estradiol in atherogenesis that may contribute to the sexual dimorphisms in cardiovascular disease observed in human patients.https://www.mdpi.com/1422-0067/25/2/951macrophage polarization17β-estradioltestosterone |
| spellingShingle | Sophie Enright Geoff H. Werstuck Investigating the Effects of Sex Hormones on Macrophage Polarization International Journal of Molecular Sciences macrophage polarization 17β-estradiol testosterone |
| title | Investigating the Effects of Sex Hormones on Macrophage Polarization |
| title_full | Investigating the Effects of Sex Hormones on Macrophage Polarization |
| title_fullStr | Investigating the Effects of Sex Hormones on Macrophage Polarization |
| title_full_unstemmed | Investigating the Effects of Sex Hormones on Macrophage Polarization |
| title_short | Investigating the Effects of Sex Hormones on Macrophage Polarization |
| title_sort | investigating the effects of sex hormones on macrophage polarization |
| topic | macrophage polarization 17β-estradiol testosterone |
| url | https://www.mdpi.com/1422-0067/25/2/951 |
| work_keys_str_mv | AT sophieenright investigatingtheeffectsofsexhormonesonmacrophagepolarization AT geoffhwerstuck investigatingtheeffectsofsexhormonesonmacrophagepolarization |